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Spatial niche formation but not malignant progression is a driving force for
intratumoural heterogeneity
#MMPMID27291893
Hoefflin R
; Lahrmann B
; Warsow G
; Hübschmann D
; Spath C
; Walter B
; Chen X
; Hofer L
; Macher-Goeppinger S
; Tolstov Y
; Korzeniewski N
; Duensing A
; Grüllich C
; Jäger D
; Perner S
; Schönberg G
; Nyarangi-Dix J
; Isaac S
; Hatiboglu G
; Teber D
; Hadaschik B
; Pahernik S
; Roth W
; Eils R
; Schlesner M
; Sültmann H
; Hohenfellner M
; Grabe N
; Duensing S
Nat Commun
2016[Jun]; 7
(?): ncomms11845
PMID27291893
show ga
Intratumoural heterogeneity (ITH) is a major cause of cancer-associated
lethality. Extensive genomic ITH has previously been reported in clear cell renal
cell carcinoma (ccRCC). Here we address the question whether ITH increases with
malignant progression and can hence be exploited as a prognostic marker.
Unexpectedly, precision quantitative image analysis reveals that the degree of
functional ITH is virtually identical between primary ccRCCs of the lowest stage
and advanced, metastatic tumours. Functional ITH was found to show a
stage-independent topological pattern with peak proliferative and signalling
activities almost exclusively in the tumour periphery. Exome sequencing of
matching peripheral and central primary tumour specimens reveals various
region-specific mutations. However, these mutations cannot directly explain the
zonal pattern suggesting a role of microenvironmental factors in shaping
functional ITH. In conclusion, our results indicate that ITH is an early and
general characteristic of malignant growth rather than a consequence of malignant
progression.
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